EP1112083A2 - Verwendung eines angiogenen faktors zur behandlung von mikrovaskulären angiopathien - Google Patents

Verwendung eines angiogenen faktors zur behandlung von mikrovaskulären angiopathien

Info

Publication number
EP1112083A2
EP1112083A2 EP99946776A EP99946776A EP1112083A2 EP 1112083 A2 EP1112083 A2 EP 1112083A2 EP 99946776 A EP99946776 A EP 99946776A EP 99946776 A EP99946776 A EP 99946776A EP 1112083 A2 EP1112083 A2 EP 1112083A2
Authority
EP
European Patent Office
Prior art keywords
vegf
factor
injury
angiogenic factor
angiogenic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP99946776A
Other languages
English (en)
French (fr)
Other versions
EP1112083B1 (de
Inventor
George F. Schreiner
Richard J. Johnson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Scios Inc En University Of Washington
Original Assignee
Scios LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Scios LLC filed Critical Scios LLC
Priority to EP03025732A priority Critical patent/EP1417971A3/de
Publication of EP1112083A2 publication Critical patent/EP1112083A2/de
Application granted granted Critical
Publication of EP1112083B1 publication Critical patent/EP1112083B1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1858—Platelet-derived growth factor [PDGF]
    • A61K38/1866—Vascular endothelial growth factor [VEGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Definitions

  • the invention concerns a method for the prevention or repair of injury to nonvascular tissue associated with injury to blood vessels serving the tissue, by administering an effective amount of an angiogenic factor or an agonist thereof, or a factor stimulating the production of an angiogenic factor.
  • the treatment preferably maintains the normal function of the organ comprising the nonvascular tissue, such as kidney, heart, or lungs.
  • the invention concerns a method for the treatment of hemolytic uremic syndrome (HUS) by administering to a patient at risk of developing or having diagnosed HUS an effective amount of an angiogenic factor, or an agonist thereof, or a factor stimulating the production of an angiogenic factor.
  • HUS hemolytic uremic syndrome
  • the invention concerns a method for the prevention or repair of injury to vascular endothelial cells, comprising introducing into such endothelial cells a polynucleotide encoding an angiogenic or cytoprotective factor, an agonist thereof, or a factor stimulating the production of an angiogenic or cytoprotective factor.
  • the angiogenic factor may, for example, be a vascular endothelial growth factor (VEGF), or a basic or acidic fibroblast growth factor (bFGF or aFGF).
  • VEGF vascular endothelial growth factor
  • bFGF or aFGF basic or acidic fibroblast growth factor
  • the VEGF preferably is hVEGF )2 i or hVEGF ⁇ , which may, for example, be in homo- or heterodimeric form, and may be partially or fully unglycosylated.
  • the angiogenic factors, such as VEGF preferably exert their activity primarily via effects other than inducing new blood vessel formation.
  • Figure 1 is a schematic representation of the various forms of VEGF generated by alternative splicing of VEGF mRNA.
  • the protein sequences encoded by each of the eight exons of the VEGF gene are represented by numbered boxes.
  • the sequences encoded by exons 6 and 7 are rich in basic amino acid residues and confer the ability to interact with heparin and heparin-like molecules. Asterisks indicate N-linked glycosylation sites.
  • Exon 1 and the first part of exon 2 (depicted by a narrower bar) encode the secretion signal sequence for the protein.
  • Figure 2 shows a nucleotide sequence encoding native human VEGF ⁇ 2I (SEQ ID NO: 1).
  • Figure 5 shows the amino acid sequence of native human VEGF ⁇ 45 (SEQ ID NO: 4).
  • a chimeric molecule consisting of one chain comprising at least a portion of the A- or B-chain subunit of a platelet-derived growth factor, disulfide linked to a second chain comprising at least a portion of a VEGF molecule. More details of such dimers are provided, for example, in U.S. Patent Nos. 5,194,596 and 5,219,739 and in European Patent EP-B 0484 401, the disclosures of which are hereby expressly incorporated by reference. The nucleotide and amino acid sequences of and bovine VEGF ]20 are disclosed, for example, in U.S. Patent Nos. 5,194,596 and 5,219,739, and in EP 0 484 401.
  • VEGF vascular endothelial growth factor
  • Covalent derivatives are also included within the meaning of functional derivatives. Covalent modifications may be introduced into the molecule by reacting targeted amino acid residues with an organic derivatizing agent that is capable of reacting with selected side chains or terminal residues. Further details of such covalent modifications are provided, for example, in U.S. Patent No. 5,332,671, the disclosure of which is hereby expressly incorporated by reference.
  • the CDRs in each chain are held together in close proximity by the FR regions and, with the CDRs from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al, NIH Publ. No.91-3242, Vol. I, pages 647-669 (1991)).
  • the constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in antibody-dependent cellular toxicity.
  • “Framework” or "FR” residues are those variable domain residues other than the hypervariable region residues as herein defined.
  • antibody is used herein in the broadest sense and specifically covers, without limitation, intact monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g. bispecific antibodies) formed from at least two intact antibodies, and antibody fragments so long as they exhibit the desired biological activity.
  • the term "monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen.
  • the modifier "monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
  • the culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the particular angiogenic factor used, such as VEGF.
  • the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA).
  • RIA radioimmunoassay
  • ELISA enzyme-linked immunoabsorbent assay
  • the binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem.. 107:220 (1980).
  • the methods of the present invention further useful in the preservation or enhancement of function of organ allografts, including but not restricted to transplants of kidney, heart, liver, lung, pancreas, skin, bone, intestine, and xenografts.
  • Pharmaceutically acceptable salts include acid addition salts such as those containing sulfate, hydrochloride, phosphate, sulfonate, sulfamate, sulfate, acetate, citrate, lactate, tartrate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclolexylsulfonate, cyclohexylsulfamate and quinate.
  • acid addition salts such as those containing sulfate, hydrochloride, phosphate, sulfonate, sulfamate, sulfate, acetate, citrate, lactate, tartrate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclolexylsulfonate, cyclohe
  • VEGF stimulates remodeling and tissue repair in a model of TMA

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Diabetes (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Transplantation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP99946776A 1998-09-09 1999-09-09 Verwendung eines angiogenen faktors zur behandlung von mikrovaskulären angiopathien Expired - Lifetime EP1112083B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP03025732A EP1417971A3 (de) 1998-09-09 1999-09-09 Verwendung eines angiogenen Faktors zur Behandlung von mikrovaskulären Angiopathien

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US9969498P 1998-09-09 1998-09-09
US99694P 1998-09-09
US12640699P 1999-03-26 1999-03-26
US126406P 1999-03-26
US12661599P 1999-03-27 1999-03-27
US126615P 1999-03-27
PCT/US1999/020480 WO2000013702A2 (en) 1998-09-09 1999-09-09 Use of an angiogenic factor for the treatment of microvascular angiopathies

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP03025732A Division EP1417971A3 (de) 1998-09-09 1999-09-09 Verwendung eines angiogenen Faktors zur Behandlung von mikrovaskulären Angiopathien

Publications (2)

Publication Number Publication Date
EP1112083A2 true EP1112083A2 (de) 2001-07-04
EP1112083B1 EP1112083B1 (de) 2003-11-12

Family

ID=27378887

Family Applications (2)

Application Number Title Priority Date Filing Date
EP99946776A Expired - Lifetime EP1112083B1 (de) 1998-09-09 1999-09-09 Verwendung eines angiogenen faktors zur behandlung von mikrovaskulären angiopathien
EP99968631A Expired - Lifetime EP1109571B1 (de) 1998-09-09 1999-09-09 Methoden zur behandlung der salzabhängigen hypertonie

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP99968631A Expired - Lifetime EP1109571B1 (de) 1998-09-09 1999-09-09 Methoden zur behandlung der salzabhängigen hypertonie

Country Status (13)

Country Link
US (3) US6352975B1 (de)
EP (2) EP1112083B1 (de)
JP (2) JP2002524421A (de)
AT (2) ATE260675T1 (de)
AU (2) AU5910599A (de)
BR (2) BR9913564A (de)
CA (2) CA2340320C (de)
DE (2) DE69912815T2 (de)
DK (2) DK1112083T3 (de)
ES (2) ES2211165T3 (de)
IL (2) IL141687A0 (de)
PT (2) PT1109571E (de)
WO (2) WO2000013703A2 (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113418940A (zh) * 2021-06-24 2021-09-21 电子科技大学 一种基于x射线示踪颗粒的检测方法及检测装置

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US6352975B1 (en) * 1998-09-09 2002-03-05 Scios Inc. Methods of treating hypertension and compositions for use therein
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IL148674A0 (en) * 1999-11-02 2002-09-12 Genentech Inc Modulation of enos activity and therapeutic uses thereof
US7078382B1 (en) 1999-11-02 2006-07-18 Genentech, Inc. Modulation of eNOS activity and therapeutic uses thereof
US20030129251A1 (en) 2000-03-10 2003-07-10 Gary Van Nest Biodegradable immunomodulatory formulations and methods for use thereof
US7129222B2 (en) * 2000-03-10 2006-10-31 Dynavax Technologies Corporation Immunomodulatory formulations and methods for use thereof
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EP1427323A4 (de) * 2001-08-20 2004-09-15 Univ Virginia Verwendung von s-nitrosothiol-signalisierung zur behandlung von störungen der atmungskontrolle
US7981863B2 (en) * 2001-09-19 2011-07-19 Neuronova Ab Treatment of Parkinson's disease with PDGF
US7795213B2 (en) 2001-12-13 2010-09-14 Posco Methods of contacting β amyloid protein with VEGF
US20030171556A1 (en) * 2001-12-13 2003-09-11 Chi-Bom Chae Beta-amyloid binding factors and inhibitors thereof
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JP2006068401A (ja) * 2004-09-03 2006-03-16 Kyushu Institute Of Technology 人工血管
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US7893244B2 (en) * 2005-04-12 2011-02-22 Intradigm Corporation Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases
US8440619B2 (en) * 2005-08-31 2013-05-14 National University Corporation Kagawa University Utilization of hypertension/hypercardia-preventing effect of D-allose
ES2600781T3 (es) * 2008-12-04 2017-02-10 Curna, Inc. Tratamiento para enfermedades relacionadas con el factor de crecimiento del endotelio vascular (vegf) mediante la inhibición de transcritos antisentido naturales de vegf
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Cited By (1)

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Publication number Priority date Publication date Assignee Title
CN113418940A (zh) * 2021-06-24 2021-09-21 电子科技大学 一种基于x射线示踪颗粒的检测方法及检测装置

Also Published As

Publication number Publication date
IL141687A0 (en) 2002-03-10
WO2000013702A3 (en) 2000-09-08
CA2340728C (en) 2007-11-27
WO2000013702A2 (en) 2000-03-16
CA2340320A1 (en) 2000-03-16
JP2002532382A (ja) 2002-10-02
DE69912815T2 (de) 2004-10-21
CA2340728A1 (en) 2000-03-16
JP2002524421A (ja) 2002-08-06
BR9913564A (pt) 2001-05-22
ES2211165T3 (es) 2004-07-01
ATE260675T1 (de) 2004-03-15
DE69915310T2 (de) 2005-03-10
US20020193288A1 (en) 2002-12-19
WO2000013703A2 (en) 2000-03-16
IL141686A0 (en) 2002-03-10
ATE253934T1 (de) 2003-11-15
BR9913533A (pt) 2001-06-05
DK1109571T3 (da) 2004-06-21
DK1112083T3 (da) 2004-03-08
EP1109571B1 (de) 2004-03-03
AU5910599A (en) 2000-03-27
DE69912815D1 (de) 2003-12-18
CA2340320C (en) 2006-11-14
EP1112083B1 (de) 2003-11-12
US6352975B1 (en) 2002-03-05
EP1109571A2 (de) 2001-06-27
ES2216630T3 (es) 2004-10-16
AU6028599A (en) 2000-03-27
PT1109571E (pt) 2004-05-31
DE69915310D1 (de) 2004-04-08
WO2000013702A9 (en) 2000-10-19
WO2000013703A3 (en) 2000-07-06
PT1112083E (pt) 2004-03-31
US20040224885A1 (en) 2004-11-11
WO2000013703A9 (en) 2000-06-02

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